Chisenga Caroline C, Filteau Suzanne, Siame Joshua, Chisenga Molly, Prendergast Andrew J, Kelly Paul
Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia; NUSTART project, University Teaching Hospital, Lusaka, Zambia.
NUSTART project, University Teaching Hospital, Lusaka, Zambia; London School of Hygiene & Tropical Medicine, London, United Kingdom.
PLoS One. 2015 Jun 17;10(6):e0129928. doi: 10.1371/journal.pone.0129928. eCollection 2015.
To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets.
This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test.
Among 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group.
Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention.
评估赞比亚开始抗逆转录病毒治疗（ART）患者的T细胞亚群的预后价值，并评估营养干预对T细胞亚群的影响。
这是一项针对开始接受ART的营养不良成年人进行营养干预的随机临床试验的子研究。2012年4月至12月招募了随机对照试验（NUSTART试验）的参与者。参与者接受了含脂质的营养补充剂，有的还额外补充了维生素和矿物质。在基线时进行免疫表型分析，对于存活者，在ART治疗12周后进行免疫表型分析，使用标记物CD3、CD4、CD8、CD45RA、CCR7、CD28、CD57、CD31、α4β7、Ki67、CD25和HLA-DR来表征T细胞亚群。进行单变量和多变量生存分析，并使用Wicoxon秩和检验分析治疗反应。
在181名成年人中，36名（20%）在开始ART治疗12周内死亡。在单变量分析中，与存活者相比，死亡患者的增殖性CD4+T细胞较少、初始CD4+T细胞较多且肠道归巢CD4+T细胞较少；衰老的CD8+T细胞较多且增殖性CD8+T细胞较少。在多变量Cox回归模型中，高比例初始CD4+、低比例增殖性CD4+、高比例衰老CD8+和低比例增殖性CD8+亚群与死亡风险增加独立相关。与对照组相比，干预组在招募至ART治疗12周期间，近期CD4+胸腺迁出细胞增加较少。
特定的CD4+T细胞亚群对赞比亚开始接受ART治疗的患者具有相当大的预后意义，但只有胸腺输出对这种营养干预有反应。
